Human patients with Gilbert's type I syndrome and Bolivian squirrel monkeys (BoSqm's) (Saimiri sciureus) both exhibit a marked fasting hyperbilirubinemia (FH), reduced hepatic UDPG-transferase activity, reduced hepatic clearance of unconjugated bilirubin (BR), and a decreased BR diglucuronide to monoglucuronide ratio in bile. BoSM's represent the first animal model for Gilbert's syndrome in which the BR transport defect can be studied. The previous observation that hepatic BR clearance is only defective during fasting will be confirmed by measuring both the respiratory carbon monoxide and endogenous BR excretion rates as measures of heme catabolic rates. Any overproduction of BR during fasting will also be correlated with the hepatic heme oxygenase (HO) activity, blood glucose and glucagon levels. The source of increased BR (whether hepatic or erythropoietic) in bile during fasting will be determined by "early-labeled" peak analysis following 14-C-aminolevulinic acid and 14-C-glycine injection. Livers of fasted BoSM's will be isolated and perfused to determine whether transmembrane flux of BR is altered or if defective clearance is due to circulating competitors or cellular metabolic differences. Fasted BoSqM's livers will also be checked for UDPGA-transferase activities and UDPGA availability before and after glucose infusion. A special attempt will be made to test the theory that FH in this Gilbert-like syndrome may in part result from an inherited exaggeration of the metabolic effects of fasting: hypoglycemia leads to hyperglucagonemia leads to cyclic AMP induction of hepatic HO activity, resulting in a marked overproduction of BR.